We study genes of the rabbit immune system by techniques of molecular biology and immunology. The rabbit has a limited number of VH genes that rearrange. As in the chicken, the 3?-most VH1 gene is rearranged in most rabbit B lymphocytes. Rabbit appendix and chicken bursa of Fabricius are primary lymphoid organs where the B cell antibody repertoire develops in germinal centers mainly by a gene conversion- like process. By six weeks after birth, diversification of rearranged VH genes occurs at least in part, by gene conversion-like events in the appendix suggesting that this organ is a homologue of the avian bursa of Fabricius. We are currently studying diversification of light chains in developing rabbit appendix. In species such as mouse and human, generation of combinatorial diversity through use of different VH and VL genes in immunoglobulin VHDJH and VLJL rearrangements can be a major contributor to the primary antibody repertoire. In rabbits, the contribution of the combinatorial mechanism to heavy chain diversity is minimal as only a few VH genes are rearranged and expressed. To investigate the contribution of combinatorial diversity toward generation of the rabbit V-kappa repertoire, we constructed 5 genomic libraries from rabbit kidney DNA and 1 cDNA library from the bone marrow of a 1 day old rabbit using a series of PCR based strategies. Our analyses indicate that most of the sequences that we recovered from our libraries belong to a single family and some are extremely similar. The actual number of germline V-kappa genes is potentially greater than our conservative estimate of at least 39, 28 of which we found expressed as mRNA. The germline V-kappa genes display different lengths of the coding region 3 of Cys 88 ranging from 7 to 12 amino acids, resulting in CDR3 length heterogeneity among functional V-kappa-J-kappa sequences ranging from 8 to 15 amino acids. Some of the V-kappa-J-kappa junctions had N and P nucleotide additions. Thus, in contrast to limited combinatorial diversity of its heavy chain, the rabbit can draw upon a diverse set of germline V-kappa genes. The kappa light chain has the potential to be a major contributor toward generation of the antibody specificities of the rabbit pre-immune repertoire. - Rabbit, germline V-kappa genes, expressed V-kappa genes, combinatorial diversity, gene conversion, antibody repertoires.